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May 29, 2026Journal of Clinical Oncology

Transposable elements and homotypic niches as drivers of immune dynamics and resistance in melanoma epigenetic-based immunotherapy.

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Authors

TNTeresa Maria Rosaria Maria Rosaria NovielloECErika CiervoFCFrancesco Ceccarelli

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Overview

Randomized trial investigates immune dynamics and resistance in melanoma with epigenetic therapy, suggesting novel targets.

Key Points

  • This research examines how transposable elements and tumor niches influence immune response and resistance in melanoma during epigenetic therapy.
  • Phase Ib NIBIT-M4 trial (NCT02608437) evaluates guadecitabine and ipilimumab
  • Longitudinal single-cell multiome profiling using snRNA-seq and snATAC-seq on tumor biopsies
  • High-resolution spatial transcriptomics integrated with single-cell data to analyze tumor ecosystem changes.
  • Seven malignant meta-programs identified; responders showed T-cell and B-cell expansion linked to Antigen Presentation program.
  • Non-responders enriched in a Neural crest-like state, relying on spatially consolidated niches for resistance.
  • Inhibition of NFATC2 promoted re-differentiation toward immune-responsive states.

Cite This Study

Noviello et al. (2026) studied this question.

synapsesocial.com/papers/6a192ed7fab5b468c4418078https://doi.org/10.1200/jco.2026.44.16_suppl.9531
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